1. ELECTRON TRANSPORT CHAIN

2. An electron transport chain (ETC) couples electron transfer between an electron donor (such as NADH ) and an electron acceptor (such as O 2 ) with the transfer of H + ions (protons) across a membrane. The resulting electrochemical proton gradient is used to generate chemical energy in the form of adenosine triphosphate (ATP). Electron transport chains are the cellular mechanisms used for extracting energy from sunlight in photosynthesis and also from redox reactions, such as the oxidation of sugars (respiration).

3. Electron transport chains in mitochondria Most eukaryotic cells contain mitochondria, which produce ATP from products of the Krebs cycle, fatty acid oxidation, and amino acid oxidation. At the mitochondrial inner membrane, electrons from NADH and succinate pass through the electron transport chain to oxygen, which is reduced to water

4. The electron transport chain comprises an enzymatic series of electron donors and acceptors. Each electron donor passes electrons to a more electronegative acceptor, which in turn donates these electrons to another acceptor, a process that continues down the series until electrons are passed to oxygen, the most electronegative and terminal electron acceptor in the chain. Passage of electrons between donor and acceptor releases energy, which is used to generate a proton gradient across the mitochondrial membrane by actively “pumping” protons into the intermembrane space, producing a thermodynamic state that has the potential to do work. The entire process is called oxidative phosphorylation, since ADP is phosphorylated to ATP using the energy of hydrogen oxidation in many steps.

6. Energy obtained through the transfer of electrons (black arrows) down the ETC is used to pump protons (red arrows) from the mitochondrial matrix into the intermembrane space, creating an electrochemical proton gradient across the mitochondrial inner membrane (IMM) called ΔΨ. This electrochemical proton gradient allows ATP synthase (ATP-ase) to use the flow of H + through the enzyme back into the matrix to generate ATP from adenosine diphosphate (ADP) and inorganic phosphate

7. Four membrane-bound complexes have been identified in mitochondria. Each is an extremely complex transmembrane structure that is embedded in the inner membrane. Three of them are proton pumps. The structures are electrically connected by lipid-soluble electron carriers and water-soluble electron carriers. The overall electron transport chain:

8. Complex I In Complex I (NADH dehydrogenase, also called NADH:ubiquinone oxidoreductase; EC 1.6.5.3) two electrons are removed from NADH and transferred to a lipid-soluble carrier, ubiquinone (Q). The reduced product, ubiquinol (QH 2 ) freely diffuses within the membrane, and Complex I translocates four protons (H + ) across the membrane, thus producing a proton gradient. Complex I is one of the main sites at which premature electron leakage to oxygen occurs, thus being one of the main sites of production of harmful superoxide. [3] [3]

9. Complex II In Complex II (succinate dehydrogenase; EC 1.3.5.1) additional electrons are delivered into the quinone pool (Q) originating from succinate and transferred (via FAD) to Q. Complex II consists of four protein subunits: SDHA, SDHB, SDHC, and SDHD. Other electron donors (e.g., fatty acids and glycerol 3-phosphate) also direct electrons into Q (via FAD).

10. Complex III In Complex III (cytochrome bc1 complex; EC 1.10.2.2), the Q-cycle contributes to the proton gradient by an asymmetric absorption/release of protons. Two electrons are removed from QH 2 at the Q O site and sequentially transferred to two molecules of cytochrome c, a water- soluble electron carrier located within the intermembrane space. The two other electrons sequentially pass across the protein to the Q i site where the quinone part of ubiquinone is reduced to quinol. A proton gradient is formed by two quinol (4H+4e-) oxidations at the Q o site to form one quinol (2H+2e-) at the Q i site. (in total six protons are translocated: two protons reduce quinone to quinol and four protons are released from two ubiquinol molecules). When electron transfer is reduced (by a high membrane potential or respiratory inhibitors such as antimycin A), Complex III may leak electrons to molecular oxygen, resulting in superoxide formation

11. Complex IV In Complex IV (cytochrome c oxidase; EC 1.9.3.1) four electrons are removed from four molecules of cytochrome c and transferred to molecular oxygen (O 2 ), producing two molecules of water. At the same time, four protons are translocated across the membrane, contributing to the proton gradient. The activity of cytochrome c is inhibited by cyanide

12. Coupling with oxidative phosphorylation According to the chemiosmotic coupling hypothesis, proposed by Nobel Prize in Chemistry winner Peter D. Mitchell, the electron transport chain and oxidative phosphorylation are coupled by a proton gradient across the inner mitochondrial membrane. The efflux of protons from the mitochondrial matrix creates an electrochemical gradient (proton gradient). This gradient is used by the F O F 1 ATP synthase complex to make ATP via oxidative phosphorylation. ATP synthase is sometimes described as Complex V of the electron transport chain. [citation needed] The F O component of ATP synthase acts as an ion channel that provides for a proton flux back into the mitochondrial matrix. This reflux releases free energy produced during the generation of the oxidized forms of the electron carriers (NAD + and Q). The free energy is used to drive ATP synthesis, catalyzed by the F 1 component of the complex. [citation needed

13. Coupling with oxidative phosphorylation is a key step for ATP production. However, in specific cases, uncoupling the two processes may be biologically useful. The uncoupling protein, thermogenin—present in the inner mitochondrial membrane of brown adipose tissue—provides for an alternative flow of protons back to the inner mitochondrial matrix. This alternative flow results in thermogenesis rather than ATP production and generates heat. [citation needed] Synthetic uncouplers (e.g., 2,4- dinitrophenol) also exist, and, at high doses, are lethal. [citation needed]